Session Information

Background/Purpose: Fenebrutinib (GDC-0853, FEN) is an oral, non-covalent, and highly selective inhibitor of Bruton’s tyrosine kinase (BTK) in clinical development for autoimmune diseases. The efficacy, safety, and pharmacodynamic effects of fenebrutinib in patients with moderate-to-severe systemic lupus erythematosus (SLE) activity were assessed in this Phase 2, randomized, placebo-controlled, multi-center study.

Methods: Patients who met SLICC or revised ACR SLE criteria, had ≥1 serologic marker of SLE (ANA, anti-dsDNA, or anti-Smith), SLEDAI ≥6 (later amended to ≥8) at screening, and were on ≥1 standard of care (SOC) therapy (corticosteroid, antimalarial, and/or immunosuppressive) were included; patients with renal or CNS involvement, recent exposure to B cell depleting therapy, or who were receiving a calcineurin inhibitor were excluded. Enrolled patients were randomized to placebo, FEN 150 mg QD, or FEN 200 mg BID, for 48 weeks of therapy. Corticosteroid taper was recommended, with burst and taper permitted from week 0 to week 12 (W0 to W12) and W24 to W36. SRI-4 at W48 was the primary endpoint, comparing the FEN arms with placebo using a sample size of 240 patients targeted for 88% power. BICLA response at W48 was a secondary endpoint.